Engineering functional nanoparticles using libraries of polymers

药物输送领域在化学、纳米技术和生物学的前沿蓬勃发展。从理论上讲，纳米颗粒可以封装活性成分并增强其效果，从而使其充分发挥作用。尽管材料科学和工程取得了重大进展，但许多基本因素减缓了纳米材料的发展。在这项研究计划中，我们建议开发使能技术来解决这些问题。 由于一个水滴中可以容纳超过1000亿个纳米粒子，因此在该尺寸范围内组织结构是一件复杂的事情。目前，充分封装药物或成像分子的纳米颗粒的制备和优化是一个耗时的过程。总装载量、封装效率和承运人在到达目的地之前保留有效载荷的能力等因素都必须考虑在内。在此，我们建议开发新的，强大的技术，以促进在体外表征的纳米粒子。这些方法将使新设计的混合共聚物库的调查，促进有效载荷的封装。 本研究的第一个目标是设计能够简化纳米颗粒的纯化和体外评价的材料。通过增加这些程序的吞吐量，我们将促进大量纳米颗粒候选物的并行研究，并使库方法的使用能够解决具有挑战性的问题。该计划的第二个目标是使用这些使能技术来评估新设计的对特定分子表现出亲和力的共聚物库。这种材料可以自组装成具有高封装能力的纳米颗粒，潜在地解决了纳米颗粒制备和有效载荷封装中的问题。 通过对目前可用的纯化方法进行公正的评估，更重要的是开发材料体外表征技术，我们将为该领域的研究人员提供有用的知识，并为他们提供新的替代方案来面对当前的限制。这些进步将为程序的标准化铺平道路，这是一个可以大大加速转化技术发展的因素。与此同时，开发一个多功能的，可生物降解的共聚物，表现出改善的各种有效载荷的亲和力库将促进范式改变生物医学技术的发展。总之，这些因素将有助于新技术平台的出现，建立我的研究团队作为该领域的领导者，并允许在生物医学纳米技术领域培养高素质的人才。

The field of drug delivery thrives at the frontier of chemistry, nanotechnology and biology. In theory, nanoparticles can encapsulate active ingredients and potentiate their effect so they reach their targets with full potential. Despite significant advances in materials science and engineering, many fundamental considerations slow down the development of nanomaterials. In this research program, we propose to develop enabling technologies to tackle these problems. Since more than one hundred billion nanoparticles can fit inside a droplet of water, organizing architectures in that size range is a complex matter. Currently, the preparation and optimization of nanoparticles that adequately encapsulate drugs or imaging molecules is a time consuming process. Factors like total loading, encapsulation efficiency, and the carrier’s capacity to retain its payload until it reaches destination, must all be taken into consideration. Herein, we propose to develop novel, robust technologies to facilitate in vitro characterization of nanoparticles. These methods will enable the investigation of a library of newly designed hybrid copolymers that facilitate encapsulation of payloads. The first objectives of this research is to design materials that can streamline the purification and in vitro evaluation of nanoparticles. By increasing the throughput of these procedures, we will facilitate the parallel investigation of large numbers of nanoparticle candidates, and enable the use of library approaches to solve challenging issues. The second objective of the program is to use those enabling technologies to evaluate a library of newly designed copolymers exhibiting affinity for specific molecules. Such materials could self-assemble into nanoparticles with high encapsulation capacities, potentially resolving issues in nanoparticle preparation and payload encapsulation. By offering an unbiased evaluation of the purification approaches that are currently available, and, more importantly developing technologies for the in vitro characterization of materials, we will provide useful knowledge to researchers in the field, and provide them with novel alternatives to face the current limitations. These advances will pave the way toward standardization of the procedures, a factor that could seriously accelerate the development of translational technologies. In parallel, the development of a library of versatile, biodegradable copolymers that exhibit improved affinity for various payloads will facilitate the development of paradigm-changing biomedical technologies. Altogether, these elements will contribute to emergence of novel technology platforms, establish my research team as leaders in the field and allow the training of highly qualified personnel in the field of biomedical-nanotechnology.